scholarly journals Cycles of gene expression and genome response during mammalian tissue regeneration

2018 ◽  
Author(s):  
Leonor Rib ◽  
Dominic Villeneuve ◽  
Viviane Praz ◽  
Nouria Hernandez ◽  
Nicolas Guex ◽  
...  

AbstractBackgroundCompensatory liver hyperplasia — or regeneration — induced by two-thirds partial hepatectomy (PH) permits the study of synchronized activation of mammalian gene expression, particularly in relation to cell proliferation. Here, we measured genomic transcriptional responses and mRNA accumulation changes after PH and sham surgeries.ResultsDuring the first 10–20 hours, the PH- and sham-surgery responses were very similar, including parallel early activation of cell-division-cycle genes. After 20 hours, however, whereas post-PH livers continued with a robust and coordinate cell-division-cycle gene-expression response before returning to the resting state by one week, sham-surgery livers returned directly to a resting gene-expression state. Localization of RNA polymerase II (Pol II), and trimethylated histone H3 lysine 4 (H3K4me3) and 36 (H3K36me3) on genes dormant in the resting liver and activated during the PH response revealed a general de novo promoter Pol II recruitment and H3K4me3 increase during the early 10–20 hour phase followed by Pol II elongation and H3K36me3 accumulation in gene bodies during the later proliferation phase. H3K36me3, generally appearing at the first-internal exon, was preceded 5′ by H3K36me2; 3′ of the first-internal exon, in about half of genes H3K36me3 predominated and in the other half H3K36me2 and H3K36me3 co-existed. Further, we observed some unusual gene profiles with abundant Pol II but little evident H3K4me3 or H3K36me3 modification, indicating that these modifications are neither universal nor essential partners to Pol II transcription.ConclusionsPH and sham surgical procedures on mice reveal striking early post-operatory gene expression similarities followed by synchronized mRNA accumulation and epigenetic histone mark changes specific to PH.

2021 ◽  
Author(s):  
Eleonora Forte ◽  
Fatma Ayaloglu Butun ◽  
Christian Marinaccio ◽  
Matthew J. Schipma ◽  
Andrea Piunti ◽  
...  

HCMV establishes latency in myeloid cells. Using the Kasumi-3 latency model, we previously showed that lytic gene expression is activated prior to establishment of latency in these cells. The early events in infection may have a critical role in shaping establishment of latency. Here, we have used an integrative multi-omics approach to investigate dynamic changes in host and HCMV gene expression and epigenomes at early times post infection. Our results show dynamic changes in viral gene expression and viral chromatin. Analyses of Pol II, H3K27Ac and H3K27me3 occupancy of the viral genome showed that 1) Pol II occupancy was highest at the MIEP at 4 hours post infection. However, it was observed throughout the genome; 2) At 24 hours, H3K27Ac was localized to the major immediate early promoter/enhancer and to a possible second enhancer in the origin of replication OriLyt; 3) viral chromatin was broadly accessible at 24 hpi. In addition, although HCMV infection activated expression of some host genes, we observed an overall loss of de novo transcription. This was associated with loss of promoter-proximal Pol II and H3K27Ac, but not with changes in chromatin accessibility or a switch in modification of H3K27. Importance. HCMV is an important human pathogen in immunocompromised hosts and developing fetuses. Current anti-viral therapies are limited by toxicity and emergence of resistant strains. Our studies highlight emerging concepts that challenge current paradigms of regulation of HCMV gene expression in myeloid cells. In addition, our studies show that HCMV has a profound effect on de novo transcription and the cellular epigenome. These results may have implications for mechanisms of viral pathogenesis.


2013 ◽  
Vol 24 (2) ◽  
pp. 157-168 ◽  
Author(s):  
Nikolai Slavov ◽  
David Botstein

To survive and proliferate, cells need to coordinate their metabolism, gene expression, and cell division. To understand this coordination and the consequences of its failure, we uncoupled biomass synthesis from nutrient signaling by growing, in chemostats, yeast auxotrophs for histidine, lysine, or uracil in excess of natural nutrients (i.e., sources of carbon, nitrogen, sulfur, and phosphorus), such that their growth rates (GRs) were regulated by the availability of their auxotrophic requirements. The physiological and transcriptional responses to GR changes of these cultures differed markedly from the respective responses of prototrophs whose growth-rate is regulated by the availability of natural nutrients. The data for all auxotrophs at all GRs recapitulated the features of aerobic glycolysis, fermentation despite high oxygen levels in the growth media. In addition, we discovered wide bimodal distributions of cell sizes, indicating a decoupling between the cell division cycle (CDC) and biomass production. The aerobic glycolysis was reflected in a general signature of anaerobic growth, including substantial reduction in the expression levels of mitochondrial and tricarboxylic acid genes. We also found that the magnitude of the transcriptional growth-rate response (GRR) in the auxotrophs is only 40–50% of the magnitude in prototrophs. Furthermore, the auxotrophic cultures express autophagy genes at substantially lower levels, which likely contributes to their lower viability. Our observations suggest that a GR signal, which is a function of the abundance of essential natural nutrients, regulates fermentation/respiration, the GRR, and the CDC.


2012 ◽  
Vol 23 (10) ◽  
pp. 1986-1997 ◽  
Author(s):  
Nikolai Slavov ◽  
Edoardo M. Airoldi ◽  
Alexander van Oudenaarden ◽  
David Botstein

The respiratory metabolic cycle in budding yeast (Saccharomyces cerevisiae) consists of two phases that are most simply defined phenomenologically: low oxygen consumption (LOC) and high oxygen consumption (HOC). Each phase is associated with the periodic expression of thousands of genes, producing oscillating patterns of gene expression found in synchronized cultures and in single cells of slowly growing unsynchronized cultures. Systematic variation in the durations of the HOC and LOC phases can account quantitatively for well-studied transcriptional responses to growth rate differences. Here we show that a similar mechanism—transitions from the HOC phase to the LOC phase—can account for much of the common environmental stress response (ESR) and for the cross-protection by a preliminary heat stress (or slow growth rate) to subsequent lethal heat stress. Similar to the budding yeast metabolic cycle, we suggest that a metabolic cycle, coupled in a similar way to the ESR, in the distantly related fission yeast, Schizosaccharomyces pombe, and in humans can explain gene expression and respiratory patterns observed in these eukaryotes. Although metabolic cycling is associated with the G0/G1 phase of the cell division cycle of slowly growing budding yeast, transcriptional cycling was detected in the G2 phase of the division cycle in fission yeast, consistent with the idea that respiratory metabolic cycling occurs during the phases of the cell division cycle associated with mass accumulation in these divergent eukaryotes.


Molekul ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 37
Author(s):  
Hermansyah Hermansyah ◽  
Susilawati Susilawati

To elucidate the anti-proliferative effect of noni (Morinda citrifolia) fruit extract for a Saccharomyces cerevisiae model organism, analysis of gene expression changes related to cell cycle associated with inhibition effect of noni fruit extract was carried out. Anti-proliferative of noni fruit extract was analyzed using gene expression changes of Saccharomyces cerevisiae (strains FY833 and BY4741).  Transcriptional analysis of genes that play a role in cell cycle was conducted by growing cells on YPDAde broth medium containing 1% (w/v) noni fruit extract, and then subjected using quantitative real-time polymerase chain reaction (RT-PCR).  Transcriptional level of genes CDC6 (Cell Division Cycle-6), CDC20 (Cell Division Cycle-20), FAR1 (Factor ARrest-1), FUS3 (FUSsion-3), SIC1 (Substrate/Subunit Inhibitor of Cyclin-dependent protein kinase-1), WHI5 (WHIskey-5), YOX1 (Yeast homeobOX-1) and YHP1 (Yeast Homeo-Protein-1) increased, oppositely genes expression of DBF4 (DumbBell Forming), MCM1 (Mini Chromosome Maintenance-1) and TAH11 (Topo-A Hypersensitive-11) decreased, while the expression level of genes CDC7 (Cell Division Cycle-7), MBP1 (MIul-box Binding Protein-1) and SWI6 (SWItching deficient-6) relatively unchanged. These results indicated that gene expression changes might associate with anti-proliferative effect from noni fruit extract. These gene expressions changes lead to the growth inhibition of S.cerevisiae cell because of cell cycle defect.


1988 ◽  
Vol 89 (3) ◽  
pp. 397-403
Author(s):  
D.S. Nicholl ◽  
J.A. Schloss ◽  
P.C. John

To investigate the involvement of tubulin gene expression in controlling cell division events in Chlamydomonas reinhardtii we have measured tubulin mRNA levels during the cell cycle under different environmental conditions. In C. reinhardtii cells grown under the synchronizing conditions of 14 h of light followed by 10 h of darkness, mRNAs for tubulin and associated flagellar proteins were found to accumulate periodically with a peak just prior to cell division. This was not seen when previously synchronized cells were transferred to constant environmental conditions in a turbidostat, suggesting that dramatic changes in tubulin mRNA levels are not required for successful completion of the cell cycle. A hypothesis to explain the patterns of tubulin mRNA accumulation found under different environmental conditions is presented.


Open Biology ◽  
2012 ◽  
Vol 2 (4) ◽  
pp. 120033 ◽  
Author(s):  
S. Kelly ◽  
S. Kramer ◽  
A. Schwede ◽  
P. K. Maini ◽  
K. Gull ◽  
...  

The trypanosome genome is characterized by RNA polymerase II-driven polycistronic transcription of protein-coding genes. Ten to hundreds of genes are co-transcribed from a single promoter; thus, selective regulation of individual genes via initiation is impossible. However, selective responses to external stimuli occur and post-transcriptional mechanisms are thought to account for all temporal gene expression patterns. We show that genes encoding mRNAs that are differentially regulated during the heat-shock response are selectively positioned in polycistronic transcription units; downregulated genes are close to transcription initiation sites and upregulated genes are distant. We demonstrate that the position of a reporter gene within a transcription unit is sufficient to reproduce this effect. Analysis of gene ontology annotations reveals that positional bias is not restricted to stress–response genes and that there is a genome-wide organization based on proximity to transcription initiation sites. Furthermore, we show that the relative abundance of mRNAs at different time points in the cell division cycle is dependent on the location of the corresponding genes to transcription initiation sites. This work provides evidence that the genome in trypanosomes is organized to facilitate co-coordinated temporal control of gene expression in the absence of selective promoters.


2017 ◽  
Author(s):  
Richard Cronn ◽  
Peter C. Dolan ◽  
Sanjuro Jogdeo ◽  
Jill L. Wegrzyn ◽  
David B. Neale ◽  
...  

BackgroundPerennial growth in plants is the product of interdependent cycles of daily and annual stimuli that induce cycles of growth and dormancy. In conifers, needles are the key perennial organ that integrates daily and seasonal signals from light, temperature, and water availability. To understand the relationship between seasonal rhythms and seasonal gene expression responses in conifers, we examined diurnal and circannual needle mRNA accumulation in Douglas-fir (Pseudotsuga menziesii) needles at diurnal and circannual scales. Using mRNA sequencing, we sampled 6.1×109 microreads from 19 trees and constructed a de novo pan-transcriptome reference that includes 173,882 tree-derived transcripts. Using this reference, we mapped RNA-Seq reads from 179 samples that capture daily, seasonal, and annual variation.ResultsWe identified 12,042 diurnally-cyclic transcripts, 9,299 of which showed homology to annotated genes from other plant genomes, including angiosperm core clock genes. Annual analysis revealed 21,225 an-nually-cyclic transcripts, 17,335 of which showed homology to annotated genes from other plant genomes. The timing of maximum gene expression is associated with light quality at diurnal and photoperiod at annual scales, with two-thirds of transcripts reaching maximum expression +/− 2 hours from sunrise and sunset, and half reaching maximum expression +/− 20 days from winter and summer solstices. Comparison to published microarray-based gene expression studies in spruce (Picea) show that the rank order of expression for 760 putatively orthologous genes was significantly preserved, highlighting the generality of our findings.ConclusionsThis finding highlights the extensive annual and seasonal transcriptome variability demonstrated in conifer needles. At these temporal scales, 29% of expressed transcripts showed a significant diurnal rhythm, and 58.7% showed a significant circannual rhythm. Remarkably, thousands of genes reach their annual peak activity during winter dormancy, a time of metabolic stasis. Photoperiod appears to be a dominant driver of annual transcription patterns in Douglas-fir, and these results may be general for predicting rhythmic transcription patterns in emerging gymnosperm models.


2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Peilin Shen ◽  
Xuejun He ◽  
Lin Lan ◽  
Yingkai Hong ◽  
Mingen Lin

Abstract Purpose: As bladder cancer (BC) is very heterogeneous and complicated in the genetic level, exploring genes to serve as biomarkers and therapeutic targets is practical. Materials and methods: We searched Gene Expression Omnibus (GEO) and downloaded the eligible microarray datasets. After intersection analysis for identified differentially expressed genes (DEGs) of included datasets, overlapped DEGs were identified and subsequently analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein–Protein Interaction (PPI) and hub genes identification. Hub genes were further analyzed with mRNA expression comparation in Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) database, proteomics-based validation in The Human Protein Atlas (THPA) and survival analysis in GEO and Oncolnc database. Results: We analyzed five eligible GEO datasets and identified 76 overlapped DEGs mapped into PPI network with 459 edges which were mainly enriched in cell cycle pathway and related terms in GO and KEGG analysis. Among five identified hub genes, which are Cyclin-Dependent Kinase 1 (CDK1), Ubiquitin-Conjugating Enzyme E2 C (UBE2C), Cell Division Cycle 20 (CDC20), Microtubule Nucleation Factor (TPX2) and Cell Division Cycle Associated 8 (CDCA8); CDC20 and CDCA8 were confirmed as significant in mRNA expression comparation and proteomics-based validation. However, only CDC20 was considered prognostically significant in both GEO and Oncolnc database. Conclusions: CDC20 and CDCA8 were identified as candidate diagnostic biomarkers for BC in the present study; however, only CDC20 was validated as prognostically valuable and may possibly serve as a candidate prognostic biomarker and potential therapeutic target. Still, further validation studies are essential and indispensable.


2009 ◽  
Vol 19 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Vilmos Soós ◽  
Angela Juhász ◽  
Marnie E. Light ◽  
Johannes Van Staden ◽  
Ervin Balázs

AbstractAerosol smoke and smoke-water can break dormancy and promote seed germination of many plant species. In this study we investigated changes in gene expression after imbibition of light-sensitive Lactuca sativa L. cv. ‘Grand Rapids’ achenes with dilute smoke-water compared to water control samples kept in the dark or continuous light, using the fluorescent differential display technique. Although no difference was detected in the smoke-water versus water control samples germinated in light, smoke-water treatment resulted in the differential display of several expressed sequence tags (ESTs) when compared to water control samples kept in the dark. The most pronounced fragments isolated correspond to known genes related to germination, with functions in cell wall expansion, regulation of translation, the cell division cycle, carbohydrate metabolism and abscisic acid (ABA) regulation. Real-time polymerase chain reaction (PCR) validation revealed that the transcript abundance of the genes, HVA22, short-chain dehydrogenase/reductase and late embryogenesis abundant protein, are upregulated after smoke treatment when compared to control achenes kept in the light. The results indicate that smoke has a dual effect. On the one hand, the smoke can induce genes that may be linked to ABA action, whereas, on the other hand, it elicits a faster germination rate by inducing a similar pattern in gene expression as light treatment. Smoke effects could be manifested mainly through the induction of the cell division cycle, cell wall extension and storage mobilization.


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